Cilostazol protects against myocardial ischemia and reperfusion injury by activating transcription factor EB (TFEB). (1st May 2019)

• Record Type: Journal Article
• Authors: Li, Jiangjin; Xiang, Xiaoli; Xu, Zuo
• Is Part Of: Biotechnology and applied biochemistry. Volume 66:Number 4(2019)
• Page Start: 555
• Page End: 563
• Publication Date: 2019-05-01
• Subjects: autophagy -- cilostazol -- myocardial ischemia and reperfusion injury; Biotechnology -- Periodicals; Biochemical engineering -- Periodicals; Biochemistry -- Periodicals; Biochemistry -- Periodicals; Genetic Techniques -- Periodicals; Microbiological Techniques -- Periodicals; 660.6
• DOI: 10.1002/bab.1754
• Languages: English
• ISSNs: 0885-4513

Abstract

Abstract: Although cilostazol was proved to have antitumor biological effects, its function in myocardial ischemia and reperfusion (I/R) injury and the underlying mechanisms were not fully illustrated yet. In this study, a rat model of I/R injury was constructed and quantitative real‐time PCR, Western blot, and immunofluorescence (IF) assay were performed. Our results showed that cilostazol increased LC3 II/LC3 I ratio, reduced p62 abundance, and promoted the expressions of LAMP1, LAMP2, cathepsin B, and cathepsin D, indicating that cilostazol could activate autophagy and elevated lysosome activation. Following analysis showed that cilostazol enhanced nuclear protein expression of transcription factor EB (TFEB), an important regulator of autophagy‐lysosome pathway. Furthermore, CCI‐779, an inhibitor of TFEB, could reverse the effects of cilostazol on autophagic activity and lysosome activation. Importantly, cilostazol suppressed I/R injury‐induced apoptosis by decreasing the cleavage of caspase 3 and PARP. Enzyme‐linked immunosorbent assay showed that cilostazol reduced the serum levels of CTn1 and CK‐MB and decreased infract size caused by I/R injuries. Altogether this study suggested that cilostazol protects against I/R injury by regulating autophagy, lysosome, and apoptosis in a rat model of I/R injury. The protective mechanism of cilostazol was partially through increasing the transcriptional activity of TFEB.